The principal objectives are to evaluate the pancreatic DNA damage induced by N-gamma-(N-methyl-N-nitrosocarbamoyl)-L-2,4 diaminobutyric acid, N-nitrosobis (hydroxypropyl) amine; to study the intrachromatin distribution of DNA bound azaserine in Wistar/Lewis rats following azaserine treatment; and to attempt to compare the effects of agaritine with those of the proceding compounds in regard to its effect on pancreatic DNA. We will attempt to separately evaluate the presence of DNA damage in acinar cell and ductal cell populations from pancreas. Azaserine, MNDABA, and BHP are known pancreatic carcinogens in experimental animals. DNA damage will be evaluated utilizing alkaline sucrose gradient sedimentation of DNA from carcinogen treated animals and in vivo-in vitro assays for the presence of repair DNA synthesis following carcinogen treatment; measurement of binding of radioactive carcinogens to pancreatic DNA; and if possible identification of specific types of base damage in pancreatic DNA of carcinogen treated animals. The project will require synthesis of radioactive azaserine, MNDABA, and BHP. The feasibility of synthesis of labeled and unlabeled agaritine will be explored. The effects of carcinogens on DNA in pancreas will be compared with their effects on DNA in liver, kidney, and thymus and these results will be correlated with the incidence of tumors in these tissues as a way of evaluating the significance of observed DNA damage. In alkylation studies, DNA from rat tissues or in vivo incubations will be isolated, hydrolyzed, and chromatographed to separate abnormal nucleosides. Any abnormal bases will be characterized by mass and ultra violet spectroscopy and by co-chromatographing of alkylated bases with reference to alkylated base standards in a high pressure liquid chromatography system.